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Biomedical subjects

G A MacGregor

Publications and source records attributed to G A MacGregor.

At least 37 records · Page 2Linked to original sources
PubMed2001

In-vivo intracellular pH at rest and during exercise in patients with essential hypertension.

BACKGROUND: Several studies in isolated cells have reported that intracellular pH (pHi) in individuals with essential hypertension may be relatively alkaline compared to normotensive individuals. Such an abnormality of pHi in hypertension would be consistent with enhanced sodium-hydrogen exchanger activity and may provide potential mechanisms by which hypertension and its complications could develop. OBJECTIVES: To determine in-vivo intracellular pH of skeletal muscle at rest and during recovery from exercise-induced acidosis in hypertensive and normotensive subjects. METHODS: Using 31-phosphorus magnetic resonance spectroscopy, pHi of the dominant flexor digitorum superficialis was measured in 20 Caucasian subjects (14 male) with essential hypertension and 20 normotensive controls matched for gender, age, race and body mass index. Measurements were made at rest and during the exercise and recovery periods of a stepped incremental maximal exercise protocol. The rate of pHi recovery from exercise-induced acidosis was calculated by linear regression over the first 210 s of recovery from the pHi time plots of respective subjects. RESULTS: Mean resting pHi in the hypertensive (7.05 +/- 0.04) and normotensive groups (7.06 +/- 0.04) were not significantly different. There was a significant effect of gender on pHi: mean pHi was 7.07 +/- 0.03 in males and 7.02 +/- 0.03 in females, respectively (P < 0.0005). The mean intracellular pH achieved by exercise was 6.74 +/- 0.31 in hypertensive individuals and not significantly different in normotensive individuals (6.68 +/- 0.19; P = 0.4). The mean rate of pHi recovery in the hypertensives was 0.08 +/- 0.03 pH units/min and not significantly different in normotensives (0.08 +/- 0.02; P = 0.4). CONCLUSIONS: These results contrast with previously documented abnormalities in the control of pHi in hypertension and demonstrate the absence of major in-vivo disturbances of pHi in skeletal muscle, both at rest and during recovery from exercise-induced acidosis, in essential hypertension. Therefore, it is possible that previously documented abnormalities of pHi and activity of the exchanger may be either specific to cell type or not present under in-vivo conditions.

Exercise↗
PubMed2001

Transepithelial sodium absorption is increased in people of African origin.

Salt-sensitive hypertension is more common and has more severe consequences in urban black populations than in white populations. Increased renal sodium reabsorption through epithelial sodium channels may underlie the development of high blood pressure in black people. Increased sodium channel activity has been detected in subjects with Liddle's syndrome by nasal potential difference measurements. Nasal potential difference measurements were made in 39 black normotensive, 106 black hypertensive, 51 white normotensive, and 61 white hypertensive subjects. Blood pressure, body mass index, and 24-hour urinary sodium excretion were also measured. Maximum potential difference was significantly higher in black subjects than in white subjects (P=0.009) but was not significantly different between normotensive and hypertensive subjects after adjustment for age, gender, current smoking status, body mass index, and 24-hour urinary sodium excretion (black normotensive, -21.6+/-1.0 mV; black hypertensive, -21.5+/-0.7 mV; white normotensive, -18.5+/-1.0 mV; and white hypertensive subjects, -18.9+/-0.9 mV). Nasal potential difference did not correlate with blood pressure or biochemical variables within ethnic and blood pressure groups. Nasal potential difference, an index of nasal sodium channel activity, is greater in black than in white people but does not differ between normotensive and hypertensive groups. Increased nasal potential difference measurements may reflect generalized upregulation of sodium transport in black people compared with white people, which may help to explain the high prevalence of hypertension in black people but would not explain differences in blood pressure within separate ethnic groups.

Absorption↗
PubMed2001

Effect of salt intake on renal excretion of water in humans.

Two studies were performed to determine the quantitative relationship between salt intake and urinary volume (U(v)) in humans. In study 1, 104 untreated hypertensives were studied on the fifth day of a high- and a low-salt diet. The 24-hour U(v) was 2.2 L (urinary sodium [U(Na)] 277 mmol) on the high-salt diet and decreased to 1.3 L (P<0.001) (U(Na) 20.8 mmol) on the low-salt diet. The reduction in 24-hour U(v) was significantly related to the decrease in 24-hour U(Na) (P<0.001) and predicts that a 100-mmol/d reduction in salt intake would decrease 24-hour U(v) by 367 mL. In study 2, 634 untreated hypertensives were studied on their usual diet. There was a significant relationship between 24-hour U(v) and U(Na) (P<0.001). This predicts that a 100-mmol/d reduction in salt intake would decrease 24-hour U(v) by 454 mL. The International Study of Salt and Blood Pressure (INTERSALT) of 1731 hypertensives and 8343 normotensives on their usual diet showed that 24-hour U(v) was significantly related to U(Na) (P<0.001) and predicted that a 100-mmol/d reduction in salt intake would decrease 24-hour U(v) by 379 and 399 mL in hypertensives and normotensives, respectively. These findings document the important effect that salt intake has on U(v). The recommended reduction in salt intake in the general population is from 10 to 5 g/d. This would reduce fluid intake in the population by approximately 350 mL/d per person. This would have a large impact on the sales of soft drinks, mineral water, and beer.

Adult↗
PubMed2001

Importance of the renin system for determining blood pressure fall with acute salt restriction in hypertensive and normotensive whites.

Hypertensive (n=93) and normotensive (n=39) white individuals were given a high sodium intake of approximately 350 mmol/d for 5 days followed by a low sodium intake of 10 to 20 mmol/d for 5 days. With this acute and large reduction in salt intake, no significant change was seen in blood pressure in the normotensive individuals, but blood pressure decreased in the hypertensive individuals. Compared with normotensive subjects, hypertensive patients had a 7/7-mm Hg greater fall in blood pressure (P<0.05 for systolic and P<0.01 for diastolic, adjusted for age), with similar changes in urinary sodium excretion. From the high-salt to low-salt diet, plasma renin activity rose from 0.90 to 5.99 ng. mL(-1). h(-1) in normotensives, whereas in hypertensives it rose from 0.73 to only 3.14 ng. mL(-1). h(-1) (P<0.05 between hypertensives and normotensives). Plasma aldosterone rose by 1396 pmol/L in normotensive subjects and by 511 pmol/L in hypertensive patients (P<0.05). Significant inverse correlations were obtained for all subjects between the fall in blood pressure from the high-salt to low-salt diet and the rise in plasma renin activity and aldosterone that occurred in addition to the absolute level on the low-salt diet. These results demonstrate that the larger fall in blood pressure with an acute reduction in salt intake in hypertensives compared with normotensives is, at least in part, due to a less-responsive renin-angiotensin-aldosterone system in the hypertensive patients.

Adult↗
PubMed2001

Comparison of nasal pH values in black and white individuals with normal and high blood pressure.

Salt-sensitive hypertension is common in people of African origin, and may be caused by increased transepithelial sodium absorption. The pH of nasal secretions is negatively correlated with the difference in Na(+) concentration between nasal secretions and plasma, and may be a marker of transepithelial sodium absorption. Nasal pH was measured using a probe sited under the inferior turbinate. Measurements of nasal pH were reproducible, with a coefficient of variation of 3.3% for repeated measurements on the same day and of 2.7% between measurements on different days. Nasal pH did not correlate with nasal potential difference, a measure of transepithelial sodium absorption. Nasal pH was significantly lower in 89 black individuals (24 normotensive and 65 hypertensive) than in 51 white individuals (26 normotensive and 25 hypertensive) (black normotensive. 6.44+/-0.08; black hypertensive, 6.62+/-0.05; white normotensive, 6.91+/-0.06; white hypertensive, 6.98+/-0.06), after adjustment for age, gender, current smoking status, body mass index and 24 h urinary sodium excretion (P=0.002), but was not significantly different between the normotensive and hypertensive individuals. Nasal pH was more acidic in black than in white individuals, which may represent generalized up-regulation of sodium transport in black people. However, the lack of correlation between nasal pH and potential difference suggests that nasal pH is, at best, only weakly related to transepithelial sodium absorption. Ethnic differences in nasal pH may be of direct relevance in the airways, as many of the functions of airway surface liquid are dependent on pH.

Absorption↗
PubMed2001

Ethnic differences in erythrocyte membrane fluidity and the association with serum triacylglycerols.

The objectives of this study were to determine whether there are differences between black and white individuals with regard to the membrane fluidity of isolated erythrocytes, and/or in the relationships between membrane fluidity, gender and circulating lipids. Fluorescent polarization anisotropy, as an index of membrane fluidity, was determined using the fluorescent probe 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH) in 52 black and 52 white individuals, of whom 39 pairs were matched for age, sex and blood pressure. In the 39 matched pairs, the TMA-DPH anisotropy was significantly higher in the black (0.262+/-0.007) compared with the white (0.258+/-0.005) subjects (P<0.005). There was also a significant difference in serum lipids. Gender differences in TMA-DPH anisotropy were observed in the white but not in the black individuals. The associations between membrane fluidity and serum lipids were examined in the total group, separated according to ethnic group. Although the associations were in the same direction in both groups, the association was only significant in the white subjects (r= - 0.42; P<0.02). The ethnic difference in membrane fluidity was abolished when adjusting for serum triacylglycerols. In conclusion, ethnic differences in erythrocyte membrane fluidity, as determined by the use of TMA-DPH anisotropy, appear to be the result of ethnic differences in the level of serum triacylglycerols.

Adult↗
PubMed2000

Urinary acid-base excretion in normotensives and hypertensives of african origin.

Abnormalities in acid-base regulation have previously been reported both in hypertensive humans and animals and a link between abnormalities in renal sodium handling and acid excretion may be particularly important in black hypertensives. The objectives of this study were to compare indices of urinary acid excretion (urinary pH, ammonium and titratable acid excretion) between normotensives and hypertensive people of African origin. Measurements were carried out in 86 black individuals of African origin in a case-control design (19 normotensive; 67 hypertensive). Of these, 17 normotensive and 17 patients with essential hypertension were matched for age, sex and weight. Group comparisons were carried out by unpaired t-tests or two-way analysis of variance and group values are given as means +/- s.d. Urinary pH was significantly higher in the hypertensives both in the unmatched groups and in the matched groups. In the 17 matched pairs: urinary pH in the hypertensive individuals was 6.36 +/- 0.54 and 5.84 +/- 0. 53 in the normotensives, respectively; P = 0.007. Additionally, urinary titratable acidity was significantly lower in the hypertensives than in the normotensives (25.4 +/- 13.7 vs16.7 +/- 10. 7 mmol/24 h; P = 0.047) but there were no significant differences in urinary ammonium excretion. The mechanisms for the apparent reduction in acid excretion in the hypertensives is not clear but these results highlight the possibility that hypertension in blacks is associated with abnormalities of renal sodium and hydrogen exchange with compensatory increases in renal ammonium production.

Adult↗
PubMed2000

Lack of association of ACE/angiotensinogen genotype with renal function in autosomal dominant polycystic kidney disease.

ACE polymorphisms have recently been shown to associate with worse renal and or cardiovascular outcome, with the D allele widely reported as a risk factor for cardiovascular disease. In autosomal dominant polycystic kidney disease (ADPKD), there are conflicting reports of an association between ACE polymorphisms and disease phenotype. There are no previous reports of any association between angiotensinogen polymorphisms and clinical phenotype in ADPKD. We examined the ACE I/D and angiotensinogen M235T polymorphisms in 176 patients with ADPKD. Patients are categorized into three groups according to the reason for initial investigation. Clinical history and examination findings were recorded at the time of first referral. A cohort of 17 patients had progressive renal impairment observed after 3 or more years of follow-up. Reciprocal creatinine against time was plotted in this group. From the patient population of 176, a total of 33 patients reached end-stage renal failure (ESRF) or a serum creatinine greater than 500 microm/liter. ACE genotype and M235T polymorphism frequencies were compared across groups. Serum creatinine and presence of hypertension and onset of ESRF were taken as outcome variables; age and source of referral were taken as confounding variables. There was no association of any genotype or allele with either creatinine, inverse creatinine, hypertension, or age at end-stage renal failure. These findings do not support the proposition that ACE genotype or angiotensinogen polymorphisms are associated with a worse prognosis in patients with ADPKD.

Angiotensinogen↗
PubMed2000

"Apparent" heart failure: a syndrome caused by renal artery stenoses.

OBJECTIVE: To report on renal artery stenosis presenting as congestive heart failure. DESIGN: Case series. SETTING: Tertiary referral centre. PATIENTS: Nine hypertensive subjects (five male, four female) seen in the blood pressure unit, St George's Hospital, between 1991 and 1997 with clinical signs and symptoms of congestive cardiac failure but without overt coronary or valvar heart disease. Mean (SEM) age was 67 (3) years. Eight patients had renal artery revascularisation with percutaneous angioplasty and one had surgery. RESULTS: Renal revascularisation was followed by a large fall in blood pressure from 191/94 (7/3) to 150/75 (8/5) mm Hg two days after intervention (p < 0.01). There was also a large natriuresis and weight reduction. One week after revascularisation there was a mean loss in weight of 3.8 (0.6) kg. The largest fall in weight was seen in those patients with stenosis in a single functioning kidney. Furthermore, plasma atrial natriuretic factor fell from 120 (28) to 48 (9) pg/ml (p < 0.05; n = 6; normal value = 8.6 (0.8) pg/ml), and serum creatinine fell from 200 (37) to 140 (11) micromol/l (p < 0. 025). The clinical signs and symptoms of heart failure resolved and the diuretics were then withdrawn in all patients. On long term follow up, patients remained free from symptoms and signs of heart failure and the blood pressure was better controlled. CONCLUSIONS: In hypertensive patients with symptoms and signs of congestive heart failure who do not have obvious ischaemic or valvar heart disease, renal artery stenosis should be considered as a possible underlying cause. Relief of the stenosis can result in resolution of the apparent heart failure.

Aged↗
PubMed2000

Efficacy of candesartan cilexetil alone or in combination with amlodipine and hydrochlorothiazide in moderate-to-severe hypertension. UK and Israel Candesartan Investigators.

This multicenter study evaluated the efficacy of candesartan cilexetil, an angiotensin II type 1 receptor antagonist, used alone or in combination with amlodipine or in combination with amlodipine and hydrochlorothiazide in the treatment of patients with moderate-to-severe essential hypertension. After a 2-week, single-blind, placebo run-in period, patients entered a 12-week, open-label, dose-titration period. The candesartan cilexetil dose was increased from 8 to 16 mg once daily; amlodipine (5 mg once daily), hydrochlorothiazide (25 mg once daily), and additional medication were also added sequentially if necessary. Patients then entered a final 4-week, parallel-group, double-blind, randomized, placebo-controlled withdrawal period of candesartan alone. A total of 216 patients were recruited. After a 2-week run-in period on placebo tablets, mean sitting blood pressure (BP) was 175/108 mm Hg. At the end of the 12-week dose-titration/maintenance period, mean sitting BP fell to 141/88 mm Hg. In 67 patients who were randomized to placebo and had their candesartan withdrawn, there was a highly significant increase in mean systolic/diastolic BP (13/6 mm Hg) compared with those patients who continued with candesartan (ANCOVA, P:<0.0001). In conclusion, candesartan cilexetil is an effective BP-lowering drug when used alone or in combination with amlodipine or amlodipine plus hydrochlorothiazide in the treatment of moderate-to-severe essential hypertension. The drug was well tolerated throughout the investigation period.

Aldosterone↗